Aspergillus fumigatus strain-specific conidia lung persistence causes an allergic broncho-pulmonary aspergillosis-like disease phenotype Journal Article

Authors: Jones, J. T.; Liu, K. W.; Wang, X.; Kowalski, C. H.; Ross, B. S.; Mills, K. A. M.; Kerkaert, J. D.; Hohl, T. M.; Lofgren, L. A.; Stajich, J. E.; Obar, J. J.; Cramer, R. A.
Article Title: Aspergillus fumigatus strain-specific conidia lung persistence causes an allergic broncho-pulmonary aspergillosis-like disease phenotype
Abstract: Aspergillus fumigatus is a filamentous fungus which can cause multiple diseases in humans. Allergic broncho-pulmonary aspergillosis (ABPA) is a disease diagnosed primarily in cystic fibrosis patients caused by a severe allergic response often to long-term A. fumigatus colonization in the lungs. Mice develop an allergic response to repeated inhalation of A. fumigatus spores; however, no strains have been identified that can survive long-term in the mouse lung and cause ABPA-like disease. We characterized A. fumigatus strain W72310, which was isolated from the expectorated sputum of an ABPA patient, by whole-genome sequencing and in vitro and in vivo viability assays in comparison to a common reference strain, CEA10. W72310 was resistant to leukocyte-mediated killing and persisted in the mouse lung longer than CEA10, a phenotype that correlated with greater resistance to oxidative stressors, hydrogen peroxide, and menadione, in vitro. In animals both sensitized and challenged with W72310, conidia, but not hyphae, were viable in the lungs for up to 21 days in association with eosinophilic airway inflammation, airway leakage, serum IgE, and mucus production. W72310-sensitized mice that were recall challenged with conidia had increased inflammation, Th1 and Th2 cytokines, and airway leakage compared to controls. Collectively, our studies demonstrate that a unique strain of A. fumigatus resistant to leukocyte killing can persist in the mouse lung in conidial form and elicit features of ABPA-like disease. Copyright © 2021 Jones et al.
Keywords: controlled study; nonhuman; mouse; animal tissue; animal experiment; animal model; in vivo study; in vitro study; bacterial strain; th2 cell; hydrogen peroxide; oxidative stress; th1 cell; immunoglobulin blood level; aspergillus fumigatus; correlational study; bacterium isolation; immunoglobulin e; respiratory tract inflammation; eosinophilia; menadione; allergic bronchopulmonary aspergillosis; female; article; whole genome sequencing; cell viability assay; chronic infection; abpa; allergic broncho-pulmonary aspergillosis; strain heterogeneity
Journal Title: mSphere
Volume: 6
Issue: 1
ISSN: 2379-5042
Publisher: American Society for Microbiology  
Date Published: 2021-01-01
Start Page: e01250-20
Language: English
DOI: 10.1128/mSphere.01250-20
PUBMED: 33597172
PROVIDER: scopus
PMCID: PMC8544898
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Tobias Martin Hohl
    82 Hohl
  2. Kathleen Mills
    2 Mills